Hypocalcemia Reduces Endogenous Glucose Production in Hyperketonemic Sheep

Abstract

In previous experiments it has been shown that hyperketonemia lowered plasma glucose concentration in sheep and depressed endogenous glucose production by approximately 30%. This facilitates the onset of pregnancy toxemia. In the last trimester of gestation, hyperketonemia in sheep is often associated with hypocalcemia. There is an indication that hypocalcemia exerts an additional depressive effect on endogenous glucose production. The present study was undertaken to examine the effect in sheep of hypocalcemia on endogenous glucose production in the presence of normo- and hyperketonemia. The experiments were carried out with seven multiparous sheep during three different reproductive states, i.e., during pregnancy (10 +/- 8 d prepartum), during lactation (21 +/- 8 d postpartum), and 4 wk after weaning of the lambs. Concentration of glucose in plasma, turnover of glucose and the rate constant of glucose turnover were measured by isotope dilution during normo- and hypocalcemia and in the presence of normal and elevated beta-hydroxybutyrate (BHB) concentrations. Hypocalcemia was induced by i.v. infusions of Na2EDTA. Hyperketonemia was maintained by i.v. infusion of DL-beta-hydroxybutyrate. The experiments showed that induction of hypocalcemia: 1) induced a decline in plasma glucose concentration in all reproductive states during normo- and hyperketonemia and 2) significantly lowered endogenous production of glucose in nonpregnant hyperketonemic and in lactating normoketonemic ewes. Pregnant normoketonemic ewes were able to compensate for the hypoglycemic effect of hypocalcemia and to keep endogenous production at the normocalcemic level. We concluded that hypocalcemia does not promote the onset of pregnancy toxemia per se but will facilitate the development of the disease when it is present in combination with hyperketonemia.

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism

“…The present results of mRNA abundance of key enzymes related to hepatic gluconeogenesis (PC, glucose-6-phosphatase, mitochondrial phosphoenolpyruvate carboxykinase) are in contrast with suggestions from previous studies that indicated an inhibition of gluconeogenesis by elevated plasma BHBA concentration (Müller et al, 1984;Schlumbohm and Harmeyer, 2003). Müller et al (1984) suggested that ketone bodies probably have a direct inhibitory action on gluconeogenesis.…”

“…The unchanged insulin concentration in response to the BHBA infusion in the present study may be explained by the fact that ketone bodies represent only a modest stimulus on insulin secretion in ruminants (Jordan and Philips, 1978;Heitmann and Fernandez, 1986). Insulin obviously did not play a significant role in mediating the lowering effect of BHBA on plasma glucose concentration in sheep (Schlumbohm and Harmeyer, 2003). Decreased glucose concentration and hepatic glucose output due to the infusion of BHBA can reduce the availability of glucose for the peripheral tissues because exhausted glucose stores must be replaced by a catabolism of proteins during emergency conditions for the vital tissues, such as central nervous system (Madison et al, 1964).…”

Nutrition and Health of Dairy Animals

“…Hyperketonemia lowered plasma glucose concentration and depressed endogenous glucose production in sheep by approximately 30%, and this facilitates the onset of pregnancy toxemia (Schlumbohm & Harmeyer, 2003).…”

“…Ovine pregnancy toxemia (twin lamb disease, pregnancy disease) occurs primarily in ewes carrying more than one fetus (Andrews et al, 1996;Schlumbohm & Harmeyer, 2003). It is usually seen when the plane of nutrition has been static or falling over the last month of gestation when the requirements of the ewe are increasing to allow the growth of the fetuses (Andrews et al, 1996).…”

“…Ewes experience ketosis typically during the last month of pregnancy and is known as pregnancy toxemia (Schlumbohm & Harmeyer, 2003). Ovine pregnancy toxemia (twin lamb disease, pregnancy disease) occurs primarily in ewes carrying more than one fetus (Andrews et al, 1996;Schlumbohm & Harmeyer, 2003).…”